Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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lymphoid enhancer binding factor 1(LEF1) lymphoid enhancer binding factor 1(LEF1) Related Genes Homo sapiens
CHROMOSOME 4,
CYTOBAND 4q23-q25,
ENSEMBL_GENE_ID ENSG00000138795,
GENERIF_SUMMARY Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling., MITF-M transactivates its own promoter (M promoter) by interacting with LEF-1, wnt3a-beta catenin signaling regulates LEF-1 gene expression, direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of epithelial-mesenchymal transformation, ZEB1 plays a role in repressing E-cadherin and MUC1 in epithelial cells [ZEB-1], Nr-CAM is the gene most extensively induced by LEF1, induction of Lef/Tcf-dependent transcription in human endothelial cells by fibroblast growth factor-2, These results suggest that NLK phosphorylation on these sites contributes to the down-regulation of LEF-1/TCF transcriptional activity., Tcf/LEF1 has a role in transcriptional induction of cyclin D1, loss of expression of this transcription factor in a subset of peripheral t-cell lymphomas, Beta-catenin, Lef-1, Ets transcription factors, and the AP-1 protein c-Jun each weakly enhanced luciferase expression from an OPN promoter., Lymphoid enhancer factor/T cell factor has a role in development of colorectal cancer [review], Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation., a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos., LEF-1 expression is regulated through PITX2, LEF-1 and beta-catenin direct physical interactions, Smad-binding peptide aptamer LEF1 can be developed to selectively inhibit TGF-beta-induced gene expression., Taken together, these data suggest that LEF-1 is abundantly expressed in human tumors and the ratio of the oncogenic and the dominant negative short isoform altered not only in carcinomas but also in leukemia., LEF1 5'-untranslated region (UTR) mediates cap-independent translation; the 5'-UTR of full-length LEF1 mRNA contains a bona fide internal ribosome entry site (IRES)., LEF1, a downstream component of the Wnt signaling pathway, mediates breast cancer cell invasion, and may be regulated in part by estradiol, Involvement of LEF1 protein in the wingless type protein (WNT) signaling pathway not only regulates T cell development, but also peripheral T cell differentiation., hAR is a direct target of LEF-1/TCF transcriptional regulation in PCa cells; expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt, Akt, and PP2A, Sebaceous gland neoplasms harbor inactivating mutations in LEF1., NARF functions as a novel ubiquitin-ligase to regulate ubiquitylation and degradation of T cell factor/lymphoid enhancer factor, the biological outcome of aberrant LEF1 activation in colon cancer is directed by differential promoter activation and repression, LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with congenital neutropenia, Cooperates with SMAD4 to activate c-myc expression., Additional prolactin (PRL) regulatory elements corresponding to LEF-l and AP-1 transcription factor binding sites appear important for PRL expression., LEF-1 is a decisive transcription factor in neutrophil granulopoiesis [review], This study demonstrates that the two consensus Lef/Tcf binding elements (TBE)reported in neoplastic cells are dispensable for c-Myc regulation in normal keratinocytes, which instead use a novel TBE sequence variant., Notch1 co-opts Lef1 during the process of transformation to maintain survival of T-cell lymphomas, Re-expression of E-cadherin in HT29(US) cells restored the ability of caveolin-1 to down-regulate beta-catenin-Tcf/Lef-dependent transcription and survivin expression, as seen in HT29(ATCC) cells., These data support a role for PITX2 in cell proliferation, migration, and cell division through differential Lef-1 isoform expression and interactions with Lef-1 and beta-catenin., Marked upregulation of lymphoid enhancer-binding factor 1 (LEF-1), a transcription factor in the Wnt pathway, was found in HBsAg-expressing cells, role of Lef-1 in the biology of acute leukemia, pointing to the necessity of balanced Lef-1 expression for an ordered hematopoietic development, IL-4 stimulation possesses a negative effect on the expressions of LEF-1 and TCF-1 in primary T cells, suggesting a positive feedback effect of IL-4 on IL4 gene expression., beta-catenin acts together with Lef-1 to influence DeltaNp63 promoter activity and protein expression, Dpr1 negatively modulates the basal activity of Wnt1/beta-catenin signaling in the nucleus by keeping LEF1 in the repressive state., Id-1 is a novel PTEN inhibitor that could activate the Akt pathway and its downstream effectors, the Wnt/TCF pathway and p27(Kip1) phosphorylation, GnRH regulation of Jun transcription requires a functional interaction between TCF/LEF and beta-catenin., By reducing COX-2 expression, caveolin-1 interrupts a feedback amplification loop involving PGE(2)-induced signaling events linked to beta-catenin/Tcf/Lef-dependent transcription of tumor survival genes including cox-2 itself and survivin., LEF1 is a potential marker for androgen-independent disease and a key regulator of AR expression and prostate cancer growth and invasion. LEF1 is highly expressed in androgen-independent prostate cancer., hepatitis B surface antigen could stimulate proliferation and functional modification of hepatocytes via LEF-1 through the Wnt pathway at the pre-malignant stage, Two WNT target genes, LEF1 and HOXB9, are identified as promoters of lung adenocarcinoma metastasis and mediators of chemotactic invasion and colony outgrowth., expression of alternatively spliced Lef-1 isoforms is involved in the determination of proliferative or migratory characteristics of pancreatic carcinoma cells., Data show that elevated Snail expression by Pdcd4 knockdown leads to downregulation of E-cadherin resulting in activating beta-catenin/Tcf-dependent transcription., EWS/FLI1 binds LEF1, interfering with the formation of beta-catenin-LEF1 complexes, and thus with their transcriptional activity., LEF1 inactivation is an important step in the molecular pathogenesis of T-ALL in a subset of young children., LEF-1 binds specifically to the major histocompatibility complex class I-like protein CD1D promoter; enhanced expression of LEF1 in K562 or Jurkat cells suppresses CD1D promoter activity and downregulates endogenous CD1D transcripts., This study identified aberrant protein expression of LEF-1 specifically in chronic lymphocytic leukemia but not in normal mature B-cell subsets or after B-cell activation., LRP6-ICD interacts with AES exclusively in the nucleus and represses AES mediated TCF/LEF-1 reporter transcription., PC3 tumors are sustained by a small number of tumor-initiating cells with stem-like characteristics, including strong self-renewal and pro-angiogenic capability and marked by the expression pattern FAM65Bhigh/MFI2low/LEF1low., Lef1DeltaN binds beta-catenin, stimulates Lef/Tcf reporter activity, and promotes terminal osteoblast differentiation., HIPK2-dependent phosphorylation caused the dissociation of LEF1, TCF4, and TCF3 from a target promoter in vivo., Overexpression of LEF1 in primary colorectal carcinoma is a prognostic factor for poor survival and increased risk for liver metastasis., Alternative splicing of LEF1 exon 6 is regulated during pre-TCR signaling in thymic development and in response to activation of the JSL1 T-cell line and this is driven by the activity of CELF2., a novel interaction between the VDR and LEF1 that is mediated by the DNA-binding domain of the VDR and that is required for normal canonical Wnt signaling in keratinocytes., lymphoid enhancer-binding factor 1 identifies androgen-independent epithelium in the developing prostate, A strong promoter activity of pre-B cell stage-specific Crlz1 gene is caused by one distal LEF-1 and multiple proximal Ets sites., Melanoma cell phenotype switching behaviour is regulated by differential LEF1/TCF4 activity., Report universal nuclear overexpression of LEF1 but lack of nuclear beta-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic lymphomas., An association between the maternal genotype and the occurrence of cleft lip or palate was observed at two polymorphic loci (rs10022956 and rs10025431), while a foetal-maternal effect modulating the risk of clefting was found at locus rs10025431., identification of a variable number of tandem repeats polymorphism in IDO1 promoter and characterization of LEF-1 response elements, differentiation status of chronic lymphocytic leukemia (CLL) cells would result in loss of LEF-1 expression, The study demonstrated a novel b-catenin/ LEF1-miR-372&373-Dickkopf-1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/b-catenin signaling in human cancer cells., In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. [Review], nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2., a robust transcriptional CTNNAL1 up-regulation occurs during acute ozone-induced stress and is mediated at least in part by ozone-induced recruitments of LEF-1 and AP-2alpha to the human CTNNAL1 promoter., findings suggest that transcriptional activation of LEF1 is a mechanism of cross talk between HGF/c-Met and Wnt/beta-catenin pathways and is essential for HGF-induced tumor invasion, results suggest that assessing intracellular beta-catenin and LEF1 expression might help in patient risk stratification and outcome prediction, LEF-1 might play an important role in colon carcinogenesis by acting as a regulator., our results indicate a pivotal role of LEF-1 in the regulation of proliferation and MMP-7 transcription in breast cancer cells., miR-218 is involved in the invasive behavior of glioblastoma cells by targeting LEF1 and blocking the invasive axis., this study demonstrated that miR-449a directly targets LEF-1, which in turn affects the expression of Sox 9, ultimately leading to the proper regulation of the differentiation and chondrogenesis, Lef1 is overexpressed in human endometrial tumors, consistent with it playing a role in gland proliferation., High LEF1 expression is associated with significantly better relapse-free survival, overall survival, and event-free survival of cytogenetically normal acute myeloid leukemia patients., n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1, interaction of HCLS1 with LEF-1 is essential for G-CSF-triggered myeloid differentiation, Results suggest that NDRG2 and prenylated Rab acceptor-1 (PRA1) might act synergistically to prevent signaling of T-cell facto/beta-catenin., Nuclear LEF1 correlate with cerebral metastasis of lung adenocarcinomas., DNA-dependent protein kinase catalytic subunit is a novel interaction partner of lymphocyte enhancer factor 1., This study supports a functionally important role for LEF1 and its target genes in Burkitt's lymphoma., Studied the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epidemiology and clinical parameters of clear cell RCC (cRCC)., Results indicate that lymphoid enhancer-binding factor 1 (LEF1) contributes to the pathophysiology of acute myeloid leukemia (AML) and could be a predictor of better treatment response., High LEF1 expression is associated with prostate cancer., Our study suggests LEF1 expression in oral squamous cell carcinoma may play an important role in tumor progression and can be served as a predictor of poor prognosis for patients with oral squamous cell carcinoma., LEF1 protein was overexpressed in colon cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in vitro and in vivo., LEF1 expression is an independent prognostic factor in APL, and could be used in patients risk stratification., By beta-catenin's association with LEF1 and BCL9-2/B9L., Selenite caused CYLD upregulation via LEF1 and cIAP downregulation, both of which contribute to the degradation of ubiquitin chains on RIP1 and subsequent caspase-8 activation and colorectal tumor cell apoptosis., These results further implicate the CTNNB1/LEF1 transcriptional complex in the development of solid-pseudopapillary neoplasms of the pancreas, miR26b may act as a potential therapeutic agent in reducing cancer cell proliferation through repressing LEF1 activation of c-Myc and cyclin D1 expression, Tcf1 and Lef1 cooperate with Runx factors to achieve stable silencing of the Cd4 gene in CD8(+) T cells., Elevated TCF-1 and LEF-1 expression is characteristic of malignant gliomas, the expression of LEF1 is associated with the progression of human renal cell carcinoma and LEF1 maybe involved in the development of RCC, Increased expression of beta-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 is significantly correlated with decreased survival and poor prognosis in acral melanoma., LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma., LEF-1 expression in both basal cell adenomas and basal cell adenocarcinomas preferentially over other salivary gland tumors suggesting some utility as a diagnostic marker, Study found a negative correlation between miR-34a and LEF1 expression in prostate cancer cell lines and tumors and that miR-34a regulated epithelial-mesenchymal transition through direct binding to LEF1 mRNA 3' UTR region and silencing its translation., Proper sample processing ensured sufficient separation of positive LEF1 staining in T cells from negative staining in normal B and natural killer (NK) cells, The results describe a novel mutation in LEF1 causing dysregulation of Wnt/B catenin signaling in eyelid sebaceous cancinoma, study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus, Authors found that the N-terminus of delta-catenin bound to the middle region of LEF-1 unlike beta-catenin. Overexpressed delta-catenin entered the nucleus and inhibited LEF-1-mediated transcriptional activity in Bosc23 and DLD-1 cell lines., high LEF1 expression and mutation are associated with high-risk leukemia and our results also revealed that LEF1 high expression and/or gain-of-function mutations are involved in leukemogenesis of ALL., Overexpression of LEF1 is a favorable prognostic factor in childhood ALL., Methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression in chronic lymphocyte leukemia cells., LEF-1 and MITF regulate tyrosinase gene transcription in vitro via binding to its promoter., The results suggest a role for beta-catenin/LEF1-mediated transcription in both malignant transformation and metastasis of prostate cancer,
OFFICIAL_GENE_SYMBOL LEF1,
OMIM_DISEASE Sebaceous tumors, somatic,
SP_COMMENT alternative products:Additional isoforms seem to exist, domain:Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors., function:Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300. May play a role in hair cell differentiation and follicle morphogenesis. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). Isoform 3 lacks the CTNNB1 interaction domain and may be an antagonist for Wnt signaling., similarity:Belongs to the TCF/LEF family., similarity:Contains 1 HMG box DNA-binding domain., subcellular location:Found in nuclear bodies upon PIASG binding., subunit:Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with EP300, TLE1 and PIASG (By similarity). Binds THOC4, MDFI and MDFIC., tissue specificity:Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines.,